乳杆菌在阴道炎防治中的临床应用

乳杆菌是阴道微生态系统中的优势菌群 ,对于维持阴道微生态平衡具有重要作用。近几年的研究显示 ,乳杆菌制剂在促进阴道乳杆菌定植繁殖的同时抑制阴道致病菌生长 ,对多种阴道炎均有显著疗效 ,且无毒、副反应 ,提示乳杆菌制剂是一种安全、有效、复发率低的治疗阴道炎的药物 ,具有广阔的应用前景     

乳杆菌对维持阴道微生态平衡的作用机理

乳杆菌是阴道微生态系统中的优势菌群,目前的研究表明,乳杆菌在健康妇女阴道中的分离率最高,达50%~80%,其数量占阴道微生物的95%以上。乳杆菌通过替代、竞争排斥机制阻止致病微生物粘附于阴道上皮细胞,同时,还可分泌过氧化氢、细菌素、类细菌素和生物表面活性剂等抑制致病微生物生长,对维持阴道微生态平衡具有重要作用。     

健康女性阴道乳杆菌抑菌功能的初步研究

目的:研究健康女性阴道乳杆菌对阴道常见致病菌的抑制作用及其机制。方法:选取北京大学第一医院体检中心18～45岁的育龄期健康女性17例,从其阴道分泌物中分离、纯化乳杆菌并进行鉴定。采用spot on lawn和双层牛津杯法筛选出对粪肠球菌、微小消化链球菌、大肠埃希菌和白假丝酵母菌有抑制作用的阴道乳杆菌菌株。测定乳杆菌的生长曲线及代谢物内的乳酸含量。将乳杆菌与白假丝酵母菌共培养,观察乳杆菌菌体和菌液粗提物在抑制白假丝酵母菌的过程中各自所起的作用。结果:17例健康女性阴道分泌物中分离出23株乳杆菌,其中6株具有抑菌作用,分别是加氏乳杆菌、詹氏乳杆菌、阴道乳杆菌、卷曲乳杆菌、发酵乳杆菌和德氏乳杆菌,其中加氏乳杆菌增殖能力较强,詹氏乳杆菌最弱。6株乳杆菌代谢物内乳酸的含量不同,发酵乳杆菌最高为(2.72±0.035)mg/ml,卷曲乳杆菌和德氏乳杆菌较低,分别为(2.14±0.035)mg/ml和(2.13±0.025)mg/ml。加氏乳杆菌、詹氏乳杆菌、阴道乳杆菌的菌液、菌体及菌液粗提物均可以抑制白假丝酵母菌的生长(P≤0.05);发酵乳杆菌和德氏乳杆菌的菌液和菌体可以抑制白假丝酵母菌的生长(P≤0.05);卷曲乳杆菌对白假丝酵母菌则无抑制作用。结论:健康女性阴道乳杆菌的多个菌株均具有抑制大肠埃希菌、粪肠球菌、微小消化链球菌或白假丝酵母菌的功能。詹氏乳杆菌粗提物中细菌素类物质和过氧化氢的联合作用可以抑制白假丝酵母菌,加氏乳杆菌和阴道乳杆菌主要依靠过氧化氢起作用。乳杆菌产生的乳酸没有发挥抑菌作用。     

阴道乳杆菌分型鉴定及药物敏感实验的研究进展

乳杆菌一直被认为是正常生育期女性阴道内的优势菌群,对阴道具有重要的生物保护作用~([1]).维持阴道乳杆菌数量,稳定阴道微生态环境对保护女性健康有重要作用.然而,某些抗生素在经阴道给药时抑制了乳杆菌的生长,加重了阴道微生态的失衡,使得机体更容易感染其他病原体,因此,在治疗阴道感染性疾病时寻找对阴道乳杆菌影响小的抗生素至关重要.     

阴道乳杆菌与宫颈病变相关的研究进展

目前国内外有研究认为阴道乳杆菌的减少与宫颈病变的发生有一定的相关性,本文从拮抗病原微生物及抗肿瘤机制两方面入手,综述阴道乳杆菌与宫颈病变相关的一系列研究进展。     

乳杆菌与人乳头瘤病毒感染及宫颈病变的相关性

乳杆菌是健康女性阴道内数量最多的菌群,对于维持阴道微生态平衡起着重要的作用。乳杆菌能牢固黏附于阴道黏膜上皮,起到占位性保护作用,并且分泌乳酸,维持阴道的酸性环境,产生H2O2、细菌素、生物表面活性物质等抑菌物质,引起有益的免疫反应,从而抵挡病原微生物的感染,是女性下生殖道重要的微生物屏障。人乳头瘤病毒(HPV)感染是宫颈癌的直接致病因素,而阴道作为宫颈的毗邻器官,其微生态环境对宫颈起着重要的作用。近年来国内外很多学者研究发现以乳杆菌的减少为主的阴道微生态失衡与HPV感染、宫颈癌的发生有密切关系。乳杆菌通过产生各种代谢产物,以及激活机体免疫功能而发挥抵抗HPV感染、抑制肿瘤的作用。本文对乳杆菌与HPV感染及宫颈病变的相关性及其机制进行综述。     

正常阴道乳杆菌对6种常见抗真菌药物的体外敏感性

目的了解正常阴道乳杆菌对临床6种常用抗真菌药物的敏感性。方法选取于2009年8月至11月在北京大学第一医院妇产科门诊就诊的健康体检无阴道感染患者100例,取患者阴道分泌物,分离鉴定乳杆菌37例。应用药敏纸片法对不同抗真菌药物进行体外药物敏感性试验。结果阴道正常乳杆菌对克霉唑、氟康唑、咪康唑、伊曲康唑、制霉菌素和特比萘芬6种抗真菌药的敏感率(0～3.8%)均较低,耐药率92.3%～100%,各组间比较,差异无统计学意义(P0.05)。乳杆菌对头孢呋辛(阴性对照组)的耐药率为89.2%,与各抗真菌药组比较,差异均有统计学意义(P0.001)。乳杆菌对左氧氟沙星(阳性对照组)的敏感率(8.1%)较低,与各抗真菌药物组比较,差异均无统计学意义(P0.05)。结论常用6种抗真菌药物在有效抑制阴道假丝酵母菌的同时,对阴道正常乳杆菌的生存无明显影响。在临床外阴阴道假丝酵母菌病的治疗中,可以尝试同时应用抗真菌药和乳杆菌活菌制剂。     

产后6～8周女性阴道微生态的特征及乳杆菌比例影响因素分析

目的:探究产后女性阴道微生态特征及产后女性乳杆菌比例的影响因素.方法:收集2018年12月至2020年1月就诊于沈阳市妇婴医院,行产后复查女性864例为产后组,同期就诊健康体检女性815例为对照组.根据产后组乳杆菌比例将产后组分为乳杆菌比例正常组(n =203)及乳杆菌比例降低组(n =661).采集患者阴道分泌物行阴...     

益生菌制剂治疗阴道感染和复发

<正>健康女性阴道菌群以乳杆菌为主,同时包含少量厌氧菌及兼性厌氧菌,包括奇异菌属、棒状杆菌、动弯杆菌、普氏菌属、阴道加德纳菌、纤毛菌属、气球菌属(anaerococcus)和微单胞菌属(pepto-niphilus)等。除乳杆菌外,一些其他细菌如奇异菌属也可产生乳酸,属于潜在的益生菌或致病菌。这些细菌可使阴道p H值轻度升高。阴道菌群变化与微生态失调及疾病相关。月经、激素波动、性行为、卫生行为、新的性伴侣及阴道微生物构成变     

乳杆菌治疗复杂性阴道炎疗效观察

目的:探讨乳杆菌治疗复杂性阴道炎疗效及安全性分析。方法:将2009年12月至2010年12月我院收治的168例复杂性阴道炎患者随机分为观察组和对照组。观察组和对照组分别于每晚睡前阴道放置乳杆菌胶囊和甲硝唑,疗程为10天。结果:观察组和对照组的总有效率分别为98.8%,90.5%,差异有统计学意义(P<0.05);治疗期间,两组患者均未见任何不良反应;观察组与对照组总复发率分别为0%,9.5%,差异有统计学意义(P<0.05)。结论:乳杆菌治疗复杂性阴道炎具有安全、有效、复发率低等特点,值得临床推广应用。     

Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 to prevent or cure bacterial vaginosis among women with HIV

Objective

To assess, among women with HIV, whether long-term oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 supplementation can prevent bacterial vaginosis (BV) and enhance the cure rate of metronidazole among those with BV.

Methods

A randomized, double-blind, placebo-controlled trial conducted among 65 HIV-infected women with an aberrant microbiota (Nugent score 4-10) who were randomized to receive daily probiotics or placebo for 6 months. Those with BV (Nugent score 7-10) additionally received metronidazole for 10 days (400 mg twice daily).

Results

We did not find an enhanced cure rate of BV among women with HIV treated with adjuvant probiotics to metronidazole treatment. Among women with an intermediate vaginal flora, probiotics tended to increase the probability of a normal vaginal flora (odds ratio 2.4; P = 0.1) and significantly increased the probability of a beneficial vaginal pH (odds ratio 3.8; P = 0.02) at follow-up.

Conclusion

Supplementation of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 did not enhance the cure of BV among women living with HIV, but may prevent the condition among this population. Trial registration: NCT00536848.     

Randomized, double-blind, placebo-controlled study of oral lactobacilli to improve the vaginal flora of postmenopausal women

Objective

The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the influence of the orally administered probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on the quality of the vaginal flora in postmenopausal women.

Study design

Postmenopausal women with Nugent scores between 4 and 6 in initial vaginal swab, were randomized into two groups. Women in the intervention group received probiotic capsules containing 2.5 × 10⁹ CFU (colony forming units) each of lyophilized L. rhamnosus GR-1 and L. reuteri RC-14 and women in the control group received an oral placebo once daily, in both groups for 14 days. Final vaginal swabs were taken 1 day after the last administration of the medication. The primary efficacy variable was a change in the Nugent score between baseline and the end of the study of at least two grades in each individual patient.

Results

Seventy two women were recruited in the study, 35 assigned to the intervention group and 37 to the control group. Twenty-one of the 35 subjects (60%) in the intervention group and 6 of the 37 subjects (16%) in the control group showed a reduction in the Nugent score by at least two grades. The difference in the number of patients with improvement was highly significant (p = 0.0001). The median difference in Nugent scores between baseline and the end of the study was 3 in the intervention group and 0 in the control group (p = 0.0001).

Conclusion

Our results provide evidence for an alternative modality to restore the normal vaginal flora using specific probiotic strains administered orally.     

In vitro antagonistic effect of Lactobacillus on organisms associated with bacterial vaginosis

OBJECTIVE: To assess antagonistic properties of Lactobacillus strains isolated from the vaginas of healthy women as compared to the most common bacterial agents related to vaginosis. STUDY DESIGN: Antagonistic activity of different Lactobacillus strains isolated from the vaginas of healthy women not treated for infections with an antibiotic for the previous three months was screened using an agar slab method. The activity was tested against test organisms associated with bacterial vaginosis and/or urinary tract infections: Staphylococcus aureus, Enterococcus faecalis, Streptococcus agalactiae, Escherichia coli, Gardnerella vaginalis, Peptostreptococcus anaerobius and Prevotella bivia. RESULTS: Many of the 146 Lactobacillus strains tested exerted apparent antagonistic activities against gram-positive aerobic cocci and gram-negative rods, such as S aureus and E coli, and a marked number of Lactobacillus strains inhibited facultative bacteria, such as Gardnerella vaginalis and the anaerobes P anaerobius and P bivia. Only a few lactobacilli were able to inhibit growth of E faecalis and S agalactiae. Indicator bacteria growth inhibition probably relies upon several different complementary mechanisms. The specific indicator bacteria species determines which mechanism predominates. CONCLUSION: Lactobacillus strains taken from normal vaginal flora demonstrated antagonistic activity against a variety of bacteria related to vaginal and urinary tract infections. The specific occurrence rates of active Lactobacillus strains are different, and this difference is dependent on the indicator bacteria species.     

Studies on the effects of probiotic Lactobacillus mixture given orally on vaginal and rectal colonization and on parameters of vaginal health in women with intermediate vaginal flora

Objectives

The vaginal microflora is composed of many bacterial species and plays a major role in maintaining the balance of this complex environment. This study was conducted in order to assess the degree and persistence of the colonization of vaginal epithelium by strains from an orally administered mixture of lactobacilli, containing Lactobacillus fermentum 57A, Lactobacillus plantarum 57B and Lactobacillus gasseri 57C. We also monitored its effects on parameters of vaginal health, especially total lactobacilli counts, vaginal pH and Nugent score.

Study design

The patient group in this open study consisted of clinically healthy women with intermediate vaginal flora. Altogether 37 women were included in the study; 25 finished the full cycle consisting of 8 visits during 70 days. Lactobacillus mixture was administered as 1 × 10⁸ c.f.u. once a day for 60 days. Lactobacillus isolates collected from vaginal and rectal samples from studied women during all visits were typed using molecular methods (PFGE for L. fermentum and L. gasseri and MLST for L. plantarum). Total lactobacilli counts, vaginal pH and Nugent score were also determined during the visits.

Results

We confirmed that the ingested strains were able to reach and colonize both sites within the third and eighth visits, i.e. between the 20th and 70th days of the study. Maximal colonization was recorded between the fifth and seventh visits (31st–60th days). Moreover, ingestion of the Lactobacillus mixture was related to normalization of vaginal parameters (within 28–60 days after the initiation of the treatment). This was demonstrated by a decrease of vaginal pH and Nugent score together with an increase of total numbers of lactobacilli in the vagina and rectum. No adverse events were noted during the course of the study.

Conclusions

Oral application of the combination of the three probiotic strains derived from vaginal microbiota of healthy woman with high adherence abilities to both vaginal and colonic epithelium in vitro shows that both individual strains and their mixture can colonize vagina for some weeks, the effect of which is correlated with significant improvement of such parameters like pH and Nugent score values and total numbers of vaginal lactobacilli. This indicates that the mixture may be a good candidate for the planned double-blind, placebo-controlled randomized studies involving larger numbers of women.     

阴道乳杆菌对常见阴道假丝酵母菌抑制作用的体外试验研究

目的:观察阴道乳杆菌菌株在体外实验中对假丝酵母菌生长的抑制作用。方法:分离健康妇女阴道中常见的乳杆菌和外阴、阴道假丝酵母菌病(vulvovaginal candidiasis,VVC)患者阴道中的常见假丝酵母菌,采用96孔板混合生长抑制法观察处于生长对数期的乳杆菌对假丝酵母菌生长的抑制作用。结果:23例健康妇女阴道分泌物中分离出3种乳杆菌:嗜酸乳杆菌(La)、干酪乳杆菌(Lca)和卷曲乳杆菌(Lcr),15例VVC初发患者阴道分泌物中分离出3种假丝酵母菌:白色假丝酵母菌(Ca)、热带假丝酵母菌(Ct)和克柔假丝酵母菌(Ck)。各种乳杆菌均表现出对假丝酵母菌生长的抑制能力,La对各种假丝酵母菌的抑制能力均优于Lcr;与Lca相比,La对Ct的抑制更为明显;产H2O2的Lcr与不产H2O2的Lca对假丝酵母菌的抑制能力无显著差异。结论:各种乳杆菌表现出对假丝酵母菌生长的不同抑制能力,La对研究的3种假丝酵母菌的抑制能力均优于Lcr;与Lca相比,La的唯一优势体现在对Ct的抑制上;乳杆菌对假丝酵母菌的抑制可能不仅仅与产生H2O2能力有关。     

Efficacy of orally applied probiotic capsules for bacterial vaginosis and other vaginal infections: a double-blind,randomized, placebo-controlled study

Objective

To assess the efficacy of orally administered capsules containing the probiotics Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 (Lactogyn, JGL, Rijeka, Croatia) compared to placebo in otherwise healthy women diagnosed with bacterial vaginosis.

Study design

Randomized, double-blind, multicentric, placebo-controlled trial, including a total of 544 subjects. Included were women older than 18 years of age, diagnosed with vaginal infection. Subjects received either probiotic (395 subjects or 72.6%) or identical-looking placebo capsules (149 subjects or 27.4%,) per day over a period of 6 weeks. Six and 12 weeks after the beginning of the study, subjects underwent two additional gynecological examinations and their vaginal swabs were evaluated by a clinical cytologist.

Results

Mean follow-up period after the baseline visit was 44 days. After this period, restitution to balanced vaginal microbiota was reported in 40 subjects (26.9%) in the placebo group, compared to 243 subjects (61.5%) in the probiotic group. Differences between groups were statistically significant at p < 0.001. After the additional 6 weeks of follow up, normal vaginal microbiota were still present in more than half (51.1%) of subjects in the probiotic group, but only in around one-fifth (20.8%) of subjects who were taking placebo (p < 0.001).

Conclusion

Oral probiotics could be an alternative, side effect-free treatment for one of the most common indications in gynecology, combining the good aspects of both metronidazole and vaginal capsules.     

Prevention and treatment of vulvovaginal candidiasis using exogenous Lactobacillus

OBJECTIVE: To review literature examining exogenous Lactobacillus therapy for vulvovaginal candidiasis and to discuss recommendations for clinical practice and future research. DATA SOURCES: Computerized searches on MEDLINE and CINAHL November 2000, September 2001, and March 2002, with search terms including Lactobacillus, acidophilus, Candida, and yeast infections. STUDY SELECTION: Relevant English-language articles from the past 10 years. Unique or seminal studies included where pertinent. DATA EXTRACTION AND SYNTHESIS: Data organized under the following headings: endogenous Lactobacillus, exogenous Lactobacillus, Candida, studies of intravaginal Lactobacillus therapy for vulvovaginal candidiasis, studies of oral Lactobacillus therapy for vulvovaginal candidiasis. CONCLUSIONS: Vaginally administered or orally ingested Lactobacillus is able to colonize the vaginal ecosystem. Controlled intervention studies regarding the effect of such colonization on vulvovaginal candidiasis are promising but few. These studies had small numbers of participants, were inconsistent in the form of Lactobacillus used, and reported conflicting results. Further randomized controlled trials involving large numbers of women are imperative. In the meantime, health care providers should discuss potential benefits with affected patients while clarifying the current lack of conclusive evidence. Without further research into currently available sources and brands of Lactobacillus and without governmental regulation of supplements and their contents, however, it is difficult to make recommendations regarding appropriate product choice.     

The in vitro activity of vaginal Lactobacillus with probiotic properties against Candida

Lactobacilli, the predominant vaginal microorganisms in healthy premenopausal women, control other members of the vaginal microflora and thus protect against bacterial vaginosis and urinary tract infections. It has been claimed that some lactobacilli are also protective against Candida vaginitis. Little is known, however, about the mechanisms by which these lactobacilli can control vaginal populations of Candida and prevent vaginitis. To address this question, vaginal Lactobacillus strains with known antagonistic properties against bacteria were tested for their cell surface properties, adhesion to vaginal cell lines in vitro and antagonistic activities against Candida. A small proportion of the lactobacilli tested adhered strongly to cultured vaginal epithelial cells and inhibited growth of Candida albicans but not of C. pseudotropicalis. This anticandidal activity was in some Lactobacillus strains related to hydrogen peroxide (H2O2) production, but catalase treatment did not suppress this activity in other Lactobacillus strains, suggesting alternative mechanism(s). Moreover, tested vaginal Candida strains were resistant to relatively high concentrations of H2O2 that markedly exceeded those produced by even the most active Lactobacillus strains.